Photochemical Internalization Enhanced Macrophage Delivered Chemotherapy
Document Type
Article
Publication Date
12-6-2017
Publication Title
Photodiagnosis and Photodynamic Therapy
Volume
21
First page number:
156
Last page number:
162
Abstract
Background Macrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport. Methods Tumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS2a and laser irradiation at 670 nm. Results RAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number. Conclusion Results show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98 + DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone.
Keywords
Photochemical internalization; PCI; Macrophage drug delivery; Doxorubicin; Photodynamic therapy; PDT
Disciplines
Oncology
Language
English
Repository Citation
Shin, D.,
Christie, C.,
Ju, D.,
Nair, R. K.,
Molina, S.,
Berg, K.,
Krasieva, T. B.,
Madsen, S. J.,
Hirschberg, H.
(2017).
Photochemical Internalization Enhanced Macrophage Delivered Chemotherapy.
Photodiagnosis and Photodynamic Therapy, 21
156-162.
http://dx.doi.org/10.1016/j.pdpdt.2017.12.002